Abstract

The universality of as second messenger in living cells is achieved by a rich spectrum of spatiotemporal cellular concentration dynamics. release from internal storage compartments plays a key role in shaping cytosolic signals. Deciphering this signaling mechanism is essential for a deeper understanding of its physiological function and general concepts of cell signaling. Here, we review recent experimental findings demonstrating the stochasticity of oscillations and its relevance for modeling dynamics. The stochasticity arises by the hierarchical signal structure that carries molecular fluctuations of single channels onto the level of the cell leading to a stochastic medium as theoretically predicted. The result contradicts the current opinion of being a cellularoscillator. We demonstrate that cells use array enhanced coherence resonance to form rather regular spiking signals and that the “oscillations” carry information despite the involved stochasticity. The knowledge on the underlying mechanism also allows for determination of intrinsic properties from global observations. In the second part of the paper, we briefly survey different modeling approaches with regard to the experimental results. We focus on the dependence of the standard deviation on the mean period of the oscillations. It shows that limit cycle oscillations cannot describe the experimental data and that generic models have to include the spatial aspects of signaling.

Lead Paragraph: Cytosolic oscillations are an extensively used mechanism in eukaryotic cells to translate extracellular signals into intracellular responses. Due to different spatiotemporal dynamics,cells can control a variety of cellular processes. Intracellular oscillations have served as a representative example of a cellularoscillator for the last two decades.1,2 However, recent experimental findings have demonstrated that oscillations consist of sequences of random spikes.3–5 Here, we review the experimental findings on how molecular fluctuations given by the random opening and closing of single channels determine the global behavior of the cytosolic concentration. It turns out that spikes occur by wave nucleation and that cells use array enhanced coherence resonance (AECR) to generate regular oscillations, a mechanism predicted theoretically. Moreover, we show that despite their stochasticity oscillations carry information and how cells can regulate the information content. In the second part of the paper, different modeling approaches are studied with respect to their capability to describe the experimentally observed variability. We find that noisy limit cycle models fail to explain the cellulardynamics. We demonstrate furthermore how extended dynamical properties of spatially resolved models can fit the experimental data.

Acknowledgments:

We kindly thank R. D. Vilela and B. Lindner for providing the data of Fig. 12(d).